NCT00009620

Brief Summary

This large randomized trial tested whether phenobarbital given to a pregnant woman about to deliver a premature infant would prevent brain injuries in their newborns. Women with 24 to 32 week fetuses who were in preterm labor and were expected to deliver within 24 hrs were randomized to phenobarbital or usual care. They were treated until they deliver or the fetus reaches 33 wks gestation. Babies were followed until discharge and evaluated at 18-22 mos corrected age for neurodevelopmental outcome.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
610

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Feb 1993

Typical duration for phase_3

Geographic Reach
1 country

11 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 1993

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 1995

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 1997

Completed
4 years until next milestone

First Submitted

Initial submission to the registry

February 1, 2001

Completed
4 days until next milestone

First Posted

Study publicly available on registry

February 5, 2001

Completed
Last Updated

March 22, 2019

Status Verified

March 1, 2019

Enrollment Period

2 years

First QC Date

February 1, 2001

Last Update Submit

March 20, 2019

Conditions

Keywords

NICHD Neonatal Research NetworkExtremely Low Birth Weight (ELBW)PrematurityCerebral hemorrhagePhenobarbitalPregnancyPrenatal careIntraventricular hemorrhagePeriventricular leukomalaciaBrain injuryBrain hemorrhage

Outcome Measures

Primary Outcomes (1)

  • Neonatal intracranial hemorrhage or death

    72 hours of life

Secondary Outcomes (3)

  • Intracranial hemorrhage (grade I, II, III, or IV)

    72 hours of life

  • Periventricular leukomalacia

    72 hours of life

  • Neurodevelopmental impairment

    18 to 22 months of corrected age

Study Arms (2)

Phenobarbital

EXPERIMENTAL
Drug: Phenobarbital

Placebo

PLACEBO COMPARATOR
Drug: Saline

Interventions

10 mg of phenobarbital per kilogram of body weight intravenously over a period of 20 to 40 minutes (maximal dose, 1000 mg)

Phenobarbital
SalineDRUG

Infusion of normal sal

Placebo

Eligibility Criteria

Sexfemale
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Admission to a high risk perinatal unit or labor and delivery unit;
  • to 32 completed weeks gestation;
  • Expected delivery within 24 hrs;
  • Preterm labor or no labor with planned delivery for maternal-fetal indications;

You may not qualify if:

  • Anticipated delivery within two hours
  • Multiple congenital or chromosomal abnormalities in the fetus
  • Multiple gestation with more than two fetuses
  • Administration of phenobarbital during the pregnancy
  • Administration of indomethacin within one week before admission
  • Maternal platelet count of less than 100,000 per cubic millimeter

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

Stanford University

Palo Alto, California, 94304, United States

Location

Yale University

New Haven, Connecticut, 06504, United States

Location

George Washington University

Washington D.C., District of Columbia, 20052, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

Cincinnati Children's Medical Center

Cincinnati, Ohio, 45267, United States

Location

Case Western Reserve University, Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Brown University, Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

University of Tennessee

Memphis, Tennessee, 38163, United States

Location

Related Publications (3)

  • Shankaran S, Papile LA, Wright LL, Ehrenkranz RA, Mele L, Lemons JA, Korones SB, Stevenson DK, Donovan EF, Stoll BJ, Fanaroff AA, Oh W. The effect of antenatal phenobarbital therapy on neonatal intracranial hemorrhage in preterm infants. N Engl J Med. 1997 Aug 14;337(7):466-71. doi: 10.1056/NEJM199708143370705.

  • McCain GC, Donovan EF, Gartside P. Preterm infant behavioral and heart rate responses to antenatal phenobarbital. Res Nurs Health. 1999 Dec;22(6):461-70. doi: 10.1002/(sici)1098-240x(199912)22:63.0.co;2-t.

  • Shankaran S, Papile LA, Wright LL, Ehrenkranz RA, Mele L, Lemons JA, Korones SB, Stevenson DK, Donovan EF, Stoll BJ, Fanaroff AA, Oh W, Verter J. Neurodevelopmental outcome of premature infants after antenatal phenobarbital exposure. Am J Obstet Gynecol. 2002 Jul;187(1):171-7. doi: 10.1067/mob.2002.122445.

Related Links

MeSH Terms

Conditions

Premature BirthIntracranial HemorrhagesCerebral HemorrhageLeukomalacia, PeriventricularBrain Injuries

Interventions

PhenobarbitalSodium Chloride

Condition Hierarchy (Ancestors)

Obstetric Labor, PrematureObstetric Labor ComplicationsPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesHemorrhagePathologic ProcessesPathological Conditions, Signs and SymptomsEncephalomalaciaInfant, Premature, DiseasesInfant, Newborn, DiseasesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesCraniocerebral TraumaTrauma, Nervous SystemWounds and Injuries

Intervention Hierarchy (Ancestors)

BarbituratesPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Study Officials

  • Seetha Shankaran, MD

    Wayne State University

    STUDY DIRECTOR
  • Lu-Ann Papile, MD

    University of New Mexico

    PRINCIPAL INVESTIGATOR
  • Richard A. Ehrenkranz, MD

    Yale University

    PRINCIPAL INVESTIGATOR
  • Raymond Bain, PhD

    George Washington University

    PRINCIPAL INVESTIGATOR
  • James A. Lemons, MD

    Indiana University

    PRINCIPAL INVESTIGATOR
  • Sheldon B. Korones, MD

    University of Tennessee at Memphis

    PRINCIPAL INVESTIGATOR
  • David K. Stevenson, MD

    Stanford University

    PRINCIPAL INVESTIGATOR
  • Edward F. Donovan, MD

    Children's Hospital Medical Center, Cincinnati

    PRINCIPAL INVESTIGATOR
  • Barbara J. Stoll, MD

    Emory University

    PRINCIPAL INVESTIGATOR
  • Avroy A. Fanaroff, MD

    Case Western Reserve University

    PRINCIPAL INVESTIGATOR
  • William Oh, MD

    Brown University, Women and Infants Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
NETWORK

Study Record Dates

First Submitted

February 1, 2001

First Posted

February 5, 2001

Study Start

February 1, 1993

Primary Completion

February 1, 1995

Study Completion

February 1, 1997

Last Updated

March 22, 2019

Record last verified: 2019-03

Locations